N-alkylbenzyl-n-dodecenyl quaternary ammonium salts



United States Patent Ofiiee w 3,5 0,521 Patented Aug. 21, 1952 3,05%,521N-ALKYLBENZYL-N-DODECENYL ONIUM SALTS Warren D. Niederhauser,Huntsville, Ala, assignor to QUATE'RNARY Rohm & Haas Company,Philadelphia, Pa, 21 cor ora.

tion of Delaware N Drawing. Filed Apr. 3, 1959, Ser. No. 303,835 7Claims. (Cl. 260-247) in which X is preferably a halogen 'having anatomic weight between about 35.5 and 127, R is an alkyl group of six toeight carbon atoms, and the R groups, taken individually, representalkyl groups of no more than two carbon atoms and, takencollectively,'represent a divalent saturated aliphatic chain of four tofive atoms which jointly with the amino nitrogen forms a fivetosix-sided monoheterocyclic amine. Divalent in the above sense is to beconstrued to mean a, w divalency, that is, one valence at each end ofthe chain.

The symbol X is preferably chlorine, bromine, or iodine. Chlorine is thepreferred representation of X. it will be apparent to one skilled in theart that other anions may be satisfactorily employed such as sulfate,methylsulfate, phosphate, acetate, citrate, tartrate, and the like,which may be supplied directly or by metathesis with the halide form ofthe present compounds or by the use of an anion exchange resin.Generally, an anion having a group weight of up to about 127 is desired.

The R groups, taken singly, may represent alkyl groups of no more thantwo carbon atoms, that is, methyl or ethyl groups, in which case the Rgroups may be the same or different. The R groups, taken collectivelyand in conjunction with the amino nitrogen, may stand for a morpholino,thiamorpholino, pyrrolidinyl, or piperidino group, and these groupshaving a lower alkyl substituent, such as a methyl or ethyl group.

The symbol R represents an alkyl group of six to eight carbon atoms,that is, hexyl, heptyl, or octyl. The R" groups may be straight orbranched chains in any of the known configurations. For instance, theoctyl group may be n-octyl, isooctyl, tert-octyl, 2,4-dimethylhexyl,1,6-dimethylhexyl, 1,1,3,3-tetramethylbutyl, 2-ethylhexyl,3-propylpentyl, 2-methyl-4-ethylpentyl, and the like. The R group ispreferably in the para position on the benzene ring with respect to themethyl ring group, but it may satisfactorily be in the ortho or metaposition.

The dodecenyl group may be a straight or branched chain in any of theknown spatial configurations, including n-dodecenyl, isododecenyl,1,IO-dimethyI-Z-decenyl, 2,7-dimethyl-1-decenyl,1-ethyl-2-methyl-5-nonenyl, 4- propyl-Z-nonenyl, 5-butyl-2-octenyl,l,2-diethyl-4-octenyl, l-propyl-6-ethyl-3-heptenyl, and the like. Thedouble bond may be at any possible location. A common commercial form ofthe dodecenyl group that yields a compound of this invention that isparticularly eifective for the present purposes is tetramethyloctenyl,in which there are two methyl ,groups on each of the number five andseven carbon atoms, and the double bond is at the number two location.

The present quaternary ammonium compounds may be prepared preferably inone of two equally satisfactory ways. In one case,analkylbenzyldialkylamine is reacted with a dodecenyl halide.Alternatively, the instant compounds may be prepared by reacting adodecenyldialkylamine with an alkylbenzylhalide. These reactants, setforth above and hereinafter, used for the preparation ofthe quaternaryammonium compounds of this invention are known or prepared by knownmethods.

Typical of the reactants that may be employed in the present instance,when an alkylbenzyldialkylamine is reacted with a dodecenyl halide,include oc-tylbenzyldimethylamine, octylbenzyldiethylamine,hexylbenzyldimethylamine, heptylbenzylmethylethylamjne,hexylbenzylmorpholine, heptylbenzylpyrrolidine, octylbenzylpiperidine,octylbenzylthiamorpholine, dodecenyl chloride, dodecenyl bromide, anddodecenyl iodide. When a dodecenyldialkylamine is reacted with analkylbenzyl halide, as reactants there may be typically employeddodecenyldimethylamine, dodecenyldiethylamine, dodecenylmethyethylamine, dodecenylmorpholine, dodecenylthiamorpholine,dodecenylpyrrolidine, dodecenylpiperazine, dodecenylpiperidine,hexylbenzyl chloride, heptylbenzyl chloride, octylbeuzyl chloride,octylbenzyl bromide, and octylbenzyl iodide.

The. present quaternary ammonium compounds may be prepared by either oftwo equally satisfactory methods, as stated heretofore. The choice ofeither method is purely a matter of convenience. Both methods areconducted under essentially the same conditions. The reactants unite ona substantially equimolccular basis to produce substantiallyquantitative results.

The present reaction is consummated by bringing the reactants togetherat a reacting temperature, usually in the range of about 50 to 150 C.,with the range of about 60 to C. being preferred. It is oftenadvantageous to use the reflux temperature of the reaction mixture whensolvents are used. Reflux temperatures of up to about 225 C. and aboveare practical. The reactants may be supplied to the reaction mixture inequivalent amounts or either reactant may be slightly or greatly inexcess, as desired. An inert volatile solvent may be advantageouslyemployed, if desired. Suitable in this respect are water, acetonitrile,nitromethane, dimethylformamide, toluene, benzene, xylene, isopropanol,butanol, isopropyl ether, and the like, and mixtures thereof.

Reaction times of about two to twenty-four hours are generally employeddepending largely on the reaction temperature, solvent, and individualreactants used. The time of reaction is not critical but merelyinfluences the yield. As will be apparent to one skilled in the art, thelonger reaction times generally favor higher yields, up to a point, and,of course, some reactants combine more speedily than others. in order toassure completeness of reaction and concomitant substantiallyquantitative results, if desired, there may be determined the amount ofionizable halide formed in the reaction mixture. When the theoreticalamount of ionizable halide is present, the reaction is complete. At theconclusion of the reaction any solvent used is removed preferably bydistillation, preferably under reduced pressure. The product ispreferably washed with hexane, heptane, or the like, to remove anyunused starting material and then isolated by removing volatilecomponents, preferably under reduced pressure or on a steam bath.Recrystallization of the product may be accomplished, if desired, from asuitable solvent, such as ethyl acetate.

It is possible, and frequently advantageous, in the preparation of someof the instant compounds to first prepare the halide form, such aschloride, in a manner already set forth, and then prepare any otherdesired form Within the present definition by metathesis or ion exchangemethods. For instance, any of the present compounds in halide form maybe converted to the hydroxide form through the use of silver oxide, orthe like, and then converted to any desired anion form by acidifyingwith an acid of choice such as sulfuric, phosphoric, acetic, and otherswithin the range and spirit of this invention. As an alternative, ananion-exchange resin may be employed. Any of the present compounds, inhalide or hydroxide form, may be converted to any desired anion formthrough the use of an anion-exchange resin in the desired anion form.For instance, there may be used an insoluble, cross-linked,styrene-divinylbenzene copolymeric quaternary ammonium salt in itssulfate, phosphate, or the like, form to convert a present compound inhalide or hydroxide form to a desired form, such as sulfate, phosphate,and the like.

The quaternary ammonium compounds of this invention are gene-rally whiteto gray waxy or solid materials that are outstanding in bacteriostaticand bactericidal activity. The present compounds are especiallyeffective in controlling Micrococcus pyogenes var. aureus and Salmonellatyphosa, as determined by the standard AOAC phenol coefiicient test. Thepresent compounds give values in the range of about 300 to 650 and aboveagainst Salmonella typhosa and 715 to 1100 and above against Micrococcuspyogenes var. aareas; For instance, N octylbenzyl N dodecenyl N,Ndimethylammonium chloride gives a value of 430 against Salmonellatyphosa and 715 against Micrococcus pyogenes var. aareus and,correspondingly, N-hexylbenzyl-N-dodecenyl-N,N-dimethylarnmoniumchloride gives values of 625 and 1000. Similar results are obtained withthe other compounds of this invention. The compounds of this inventionare also effective in controlling Escherichia coli in hard water asevaluated by the standard Chambers Modification of the Weber-Black Test(Journal of the Association of Official Agricultural Chemists, volume41, No. 3, August 1958). The values obtained in the ChambersModification of the Weber-Black Test indicate, in parts per million ascalcium carbonate, the greatest water hardness at which the testedcompound will kill in 30 seconds at least 99.999% of the defined amountof Escherichia coli used. The 99.999% standard is that set by the UnitedStates Department of Public Health and is a very rigid one to achieve.The compounds of this invention in the Standard Chambers Modification ofthe Weber-Black Test consistently achieve values of 700 and more.lllustratively, N-dodecenyl N,N dimethyl N octylbenzylammonium chloridegives values of 700 to 750 in this test. The very high values in thistest against Escherichia coli in hard water are surprising in the lightof the known diminution of bactericidal properties of quaternaryammonium compounds in the presence of hard water It is unexpected andquite advantageous that the present compounds exhibit such Superioractivity against Micrococcas pyogenes var. aareus, Salmonella typhosa,and Escherichia coli in hard water. Because of such superiorbactericidal activity, one may employ a single compound of thisinvention to control at least these three bacteria at the same time,whereas the closest prior art compounds require at least two forsomewhat comparable, although actually inferior, activity. Therefore,the compounds of this invention provide a means for treatingcontaminated Waters, premises, and equipment by the use of a singlebactericide, particularly when the three aforementioned bacteria areconsidered.

The compounds of this invention also exhibit strong bacteriostatic andbactericidal activity toward S. fecalis, N. catarrhalis, B. suis, and C.welchii, among others, in a wide range of dilutions.

The compounds of this invention are useful fungicides in dilutions downto /2 ounce in 100 gallons of water and lower, particularly againstStemphyliam sarcinaeforme and Monilinia fructicola. These compoundsexethanol, to 40% soda ash, 20 to 40% sodium metasilicate, and theremainder sodium tripolyphosphate. One ounce of this formulation is usedper gallon of water. For sanitizing citrus fruit there is preferablyused one part of a present compound in 5000 parts. of water. For use indairy farms, there may be used 10% of a quaternary ammonium compound ofthis invention, 10% of octylphenoxypolyethoxyethanol, 7% of trisodiumphosphate, and 73% of Water. One ounce of this solution is used per fourgallons of water. The instant compounds in aqueous solution in amountsof about 0.5 to one ounce to one hundred pounds of dry fabric, areexcellent as a final diaper rinse to prevent diaper rash. Thesecompounds are also excellent premise sanitizers where they may beemployed in concentrations of about 0.1 to 2.0% in aqueous cleaningsolutions.

This application is a continuation-in-part of application Serial No.549,515, filed November 28, 1955, now abandoned.

The quaternary ammonium compounds of this invention and the method fortheir preparation may be more fully understood from the followingexamples which are presented by way of illustration and not by way oflimitation. Parts by weight are used throughout.

Example 1 There are added to a reaction vessel 15.5 parts ofhexylbenzyldimethylamine, 17 parts of dodecenyl chloride, and 9 parts ofacetonitrile. The reaction mixture is stirred and heated at reflux fortwelve hours. The acetonitrile is removed by distillation atreducedpressure. The product is washed with hexane. The hexane is removed bydistillation at reduced pressure leaving the product. The productcontains 8.7% chlorine (9.1% theoretical), is identified asN-hexylbenzyl-N-dodecenyl- N,N-dimethylammonium chloride, and has aformula corresponding to CH3 011 In like manner, there is prepared fromdodecenyl bromide and heptylbenzyldiethylamine, the compound having theformula A mixture of 26.1 parts of hexylbenzylmorpholine, 29.4 parts ofdodecenyl iodide, and 40 parts of isopropanol is heated at reflux forsixteen hours. The isopropanol is stripped off, leaving as the residuethe product which corresponds to the compound having the formula Thesame result is obtained by similarly reacting hexylbenzyl iodide anddodecenylmorpholine.

Example 3 There are introduced into a reaction vessel 23.9 parts ofoctylbenzyl chloride, 26.5 parts of dodecenylpiperidine, and 50 parts ofnitromethane. The mixture is heated at 75 to 85 C. for twenty hours. Thenitromethane is removed by distillation under reduced pressure. Theproduct is washted with heptane and then dried by stripping off thevolatile components. The product corresponds to the formula.

01 S I TCH2Cs 17 lir zs Analogously, there is prepared, from dodecenylbromide and hexylbenzylthiamorpholine, the compound having the formulaExample 4 CH CH In like manner, there is prepared, fromoctylbenzylmethethylamine and dodecenyl bromide, the compound having theformula CH3 Cr s Example 5 There are added to a reaction vessel 26.9parts of heptylbenzyl bromide, 23.7 parts of dodecenylpyrrolidine, and60 parts of dimethylformamide. The reaction mixture is held at 140 to146 C. for twelve hours. The dimethylformamide is removed bydistillation under reduced pressure leaving the product which has theformula The identical result is obtained by similarly reacting dodecenylbromide and heptylbenzylpyrrolidine.

Example 6 A mixture of 21.1 parts of hexylbenzyl chloride, 24 parts ofdodecenylmethylethylamine, and 50 parts of water is heated at reflux forten hours. The Water is removed by evaporation on a steam bath. Theproduct is washed with hexane and dried by distillation'under reducedpressure. The product corresponds to the formula In like manner, thereis made, from octylbenzyl bromide and dodecenyldiethylamine, thequaternary ammonium compoundsN-octylbenzyl-N-dodecenyl-N,N-diethylammonium bromide.

Example 7 There is preparedN-hexylbenzyl-N-dodecenyl-N,N-dimethylammonium phosphate by passing thecorresponding halide form of the quaternary ammonium compound through abed of chloromethylated and aminated styrene divinylbenzeneanion-exchange resin in free base form and then titrating withphosphoric acid. The same compound is prepared by first converting theanion-exchange resin to the phosphate form and then passing the chlorideform of the quaternary ammonium compound through a bed of theanion-exchange resin in phosphate form. The compound N-octylbenzyl Ndodecenyl-N,N-diethylammonium sulfate is prepared in a similar Way.

I claim:

1. As a new composition of matter, the quaternary ammonium compoundhaving the formula in which R is an alkyl group of six to eight carbonatoms, the R groups taken singly represent alkyl groups of no more thantwo carbon atoms and taken collectively represent a saturated aliphaticchain of a,w-divalency having four to five atoms which jointly with theamino nitrogen atom forms a fiveto six-sided monoheterocyclic amine fromthe class consisting of morpholino, thiamorpholino, piperidino, andpyrrolidinyl, and X is an anion from the group consisting of chloride,bromide, iodide, sulfate, methylsulfate, phosphate, acetate, citrate,and tartrate.

2. As a new composition of matter, the quaternary ammonium compoundhaving the formula 5. As a new composition of matter, N-octylbenzyl-N-dodecenyl-N,N-dimethylammonium chloride.

6. As a new composition of matter, N-octylbenzyl-N-dodecenyl-N,N-diethylammonium sulfate.

7. As a new composition of matter, N-heptylbenzyl-Ndodecenylpyrrolidinium bromide.

No references cited.

1. AS A NEW COMPOSITION OF MATTER, THE QUARTERNARY AMMONIUM COMPOUNDHAVING THE FORMULA
 4. AS A NEW COMPOSITION OF MATTER,N-HEXYLBENZYL-NDODECENYLMORPHOLINIUM IODIDE.